Document Detail


CD38-dependent ADP-ribosyl cyclase activity in developing and adult mouse brain.
MedLine Citation:
PMID:  12403647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD38 is a transmembrane glycoprotein that is expressed in many tissues throughout the body. In addition to its major NAD+-glycohydrolase activity, CD38 is also able to synthesize cyclic ADP-ribose, an endogenous calcium-regulating molecule, from NAD+. In the present study, we have compared ADP-ribosyl cyclase and NAD+-glycohydrolase activities in protein extracts of brains from developing and adult wild-type and Cd38 -/- mice. In extracts from wild-type brain, cyclase activity was detected spectrofluorimetrically, using nicotinamide-guanine dinucleotide as a substrate (GDP-ribosyl cyclase activity), as early as embryonic day 15. The level of cyclase activity was similar in the neonate brain (postnatal day 1) and then increased greatly in the adult brain. Using [14C]NAD+ as a substrate and HPLC analysis, we found that ADP-ribose is the major product formed in the brain at all developmental stages. Under the same experimental conditions, neither NAD+-glycohydrolase nor GDP-ribosyl cyclase activity could be detected in extracts of brains from developing or adult Cd38 -/- mice, demonstrating that CD38 is the predominant constitutive enzyme endowed with these activities in brain at all developmental stages. The activity measurements correlated with the level of CD38 transcripts present in the brains of developing and adult wild-type mice. Using confocal microscopy we showed, in primary cultures of hippocampal cells, that CD38 is expressed by both neurons and glial cells, and is enriched in neuronal perikarya. Intracellular NAD+-glycohydrolase activity was measured in hippocampal cell cultures, and CD38-dependent cyclase activity was higher in brain fractions enriched in intracellular membranes. Taken together, these results lead us to speculate that CD38 might have an intracellular location in neural cells in addition to its plasma membrane location, and may play an important role in intracellular cyclic ADP-ribose-mediated calcium signalling in brain tissue.
Authors:
Claire Ceni; Nathalie Pochon; Virginie Brun; Hélène Muller-Steffner; Annie Andrieux; Didier Grunwald; Francis Schuber; Michel De Waard; Frances Lund; Michel Villaz; Marie-Jo Moutin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Biochemical journal     Volume:  370     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-06     Completed Date:  2003-03-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  175-83     Citation Subset:  IM    
Affiliation:
Laboratoire Canaux Ioniques et Signalisation, INSERM EMI 9931, DRDC-CEA, 17 avenue des Martyrs, 38051 Grenoble Cedex 9, France.
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MeSH Terms
Descriptor/Qualifier:
ADP-ribosyl Cyclase / genetics,  metabolism*
Animals
Antigens, CD / genetics,  metabolism*
Antigens, CD38
Base Sequence
Blotting, Western
Calcium Signaling
Cells, Cultured
Centrifugation
DNA Primers
Hippocampus / enzymology*
Membrane Glycoproteins
Mice
Microscopy, Confocal
Microscopy, Fluorescence
NAD / metabolism
RNA, Messenger / genetics
Grant Support
ID/Acronym/Agency:
AI-43629/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/DNA Primers; 0/Membrane Glycoproteins; 0/RNA, Messenger; 53-84-9/NAD; EC 3.2.2.5/ADP-ribosyl Cyclase; EC 3.2.2.5/Antigens, CD38; EC 3.2.2.5/Cd38 protein, mouse
Comments/Corrections

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